IL-10 is considered a potent anti-inflammatory cytokine that strongly inhibits the production of inflammatory mediators. However, recent studies have suggested that IL-10 also has immunostimulatory properties on CD4+, CD8+ T cells, and/or NK cells, resulting in increased IFN-γ production which in turn may lead to related inflammatory responses in humans.
Despite encouraging pre-clinical data suggesting this cytokine as therapeutically valuable biological, results of clinical trials evaluating the merit of IL-10 administration in chronic inflammation have been preponderantly disappointing. Bulk of pre-clinical data and analysis of patients with IL-10 or IL-10 receptor defects clearly point to endogenously produced IL-10 as potent and significant anti-inflammatory determinant. However, thorough analysis further suggests that IL-10 has the potential to acquire sharply contrasting properties in an inflammatory environment in vivo. In recent years several studies have been performed in order to verify the human response upon IL-10 administration, particularly in view of its anti-inflammatory potential. Those clinically important studies disclosed perplexing pro-inflammatory functions of IL-10. However, the basis of IL-10 immunostimulatory action remains unclear.
On the other hand, IL-10 has been explored for use in the treatment of proliferative disorders, e.g., cancer, tumors, etc. IL-10 induces cytotoxic activity of CD8 T-cells, antibody production of B-cell and suppresses macrophage activity and tumor promoting inflammation. IL-10 appears to increase the infiltration of CD8+ T cells to a tumor, as well as increasing the expression of inflammatory cytokines that play a role in tumor immunity. Treatment with IL-10 may provide a significant improvement for tumor treatment.
One drawback of using IL-10 and particularly any form of recombinant IL-10 in therapy is its short serum half-life. One strategy for increasing serum half-life of a therapeutic protein such as IL-10 is to attach the protein to an Fc (fragment crystallizable) domain of an antibody. Many such fusion proteins are capable of forming homodimers or heterodimers thereby forming antibody-like fusion protein molecules.
Depending on the therapeutic application, the ability to selectively enhance either the anti-inflammatory activity or the immunostimulatory activity of IL-10 would be desired. It would also be desirable to increase the half-life of recombinant IL-10.